Hyperglycemia induces miR-26-5p down-regulation to overexpress PFKFB3 and accelerate epithelial-mesenchymal transition in gastric cancer

Gastric cancer (GC) is one of the most deadly malignancies with high morbidity worldwide. Cancer cells exhibited higher level of glucose catabolism than normal cells to meet the needs for rapid growth. Emerging evidences indicated that hyperglycemia has positive effects on the progression of tumor. As a vital regulator of glycolysis, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) was confirmed to have a higher expression level in tumor tissue and correlated with the prognosis of GC patients. However, the role of PFKFB3 in GC patients with hyperglycemia remains unclear. The data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were utilized to analyze the expression level of PFKFB3 and conducted survival analysis of GC patients. Western blot assay was used to detect gene expression at the protein level. Small interfering RNA (siRNA) transfection assay was conducted to down-regulate the expression of PFKFB3. Cell functional assays were carried out to reflect the ability of cell proliferation and migration. The results indicated that PFKFB3 was significantly upregulated and its overexpression was associated with poor prognosis of GC patients. Besides, hyperglycemia stimulated the higher expression of PFKFB3 along with the enhanced proliferation, migration and epithelial-mesenchymal transition (EMT) in GC cells. Knocking down of PFKFB3 effectively reversed the effects of high glucose concentration on GC malignant phenotype and the opposite results were gained when miR-26-5p was inhibited. Therefore, PFKFB3 down-regulated by miR-26-5p inhibited the malignant phenotype of GC with hyperglycemia.

Automated summary

This study found that the overexpression of PFKFB3 is associated with poor prognosis in gastric cancer patients. Hyperglycemia stimulates the high expression of PFKFB3 and enhances proliferation, migration, and epithelial-mesenchymal transition in gastric cancer cells. Down-regulation of PFKFB3 by miR-26-5p inhibits the malignant phenotype of gastric cancer with hyperglycemia.